Aldosterone modulates neural vasomotor response in hypertension: role of calcitonin gene-related peptide

Regul Pept. 2004 Aug 15;120(1-3):253-60. doi: 10.1016/j.regpep.2004.03.016.

Abstract

Objective: We analyse the effect of aldosterone on vasomotor response induced by electrical field stimulation (EFS) in mesenteric arteries from Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR).

Results: Aldosterone (0.001-1 microM) reduced vasoconstrictor response to EFS in a dose- and time-dependent manner only in SHR. Thus, the rest of experiments were performed only in SHR. Aldosterone did not affect either noradrenaline response or release. Effect of aldosterone (1 microM) on EFS response was not affected by NG-nitro-arginine-methyl esther (100 microM), and was abolished by capsaicin (0.5 microM) and the calcitonin gene-related peptide antagonist (CGRP 8-37, 0.5 microM). Calcitonin gene-related peptide (0.1 nM-0.1 microM) induced a concentration-dependent relaxation, which was enhanced by aldosterone (1 microM). Incubation with either spironolactone (1 microM), glibenclamide (10 microM), RU 486 10 microM, ODQ (10 microM) or cycloheximide (10 microM) significantly reduced the enhancement of CGRP-relaxation produced by aldosterone, while remained unmodified by SQ 22,536.

Conclusions: Aldosterone decreases the vasoconstrictor response to EFS in mesenteric arteries from SHR but not from WKY. This effect is mediated by an increased response to the sensory neurotransmitter CGRP, substantially, through glucocorticoid receptors activation. Furthermore, this effect is mediated by an increase of cGMP synthesis and ATP-dependent potassium channel activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / pharmacology
  • Adenosine Triphosphate / metabolism
  • Aldosterone / pharmacology*
  • Animals
  • Anti-Arrhythmia Agents / pharmacology
  • Calcitonin Gene-Related Peptide / physiology*
  • Capsaicin / pharmacology
  • Cyclic GMP / metabolism
  • Electric Stimulation
  • Enzyme Inhibitors / pharmacology
  • Glyburide / pharmacology
  • Hypertension / metabolism*
  • Hypertension / pathology
  • Male
  • Mesenteric Arteries / drug effects
  • Mesenteric Arteries / innervation
  • Mineralocorticoid Receptor Antagonists / pharmacology
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Neurons / physiology*
  • Norepinephrine / metabolism
  • Potassium Channels / metabolism
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Receptors, Glucocorticoid / metabolism
  • Spironolactone / pharmacology
  • Vasoconstriction / physiology
  • Vasomotor System / physiology*

Substances

  • Anti-Arrhythmia Agents
  • Enzyme Inhibitors
  • Mineralocorticoid Receptor Antagonists
  • Potassium Channels
  • Receptors, Glucocorticoid
  • 9-(tetrahydro-2-furyl)-adenine
  • Spironolactone
  • Aldosterone
  • Adenosine Triphosphate
  • Cyclic GMP
  • Adenine
  • Calcitonin Gene-Related Peptide
  • Capsaicin
  • Glyburide
  • NG-Nitroarginine Methyl Ester
  • Norepinephrine